rs11166965

Variant names:

• chr8-140252916-G-A
• rs11166965
• NM_001160372.4:c.2292C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001160372.4(TRAPPC9):​c.2292C>T​(p.Gly764Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,613,104 control chromosomes in the GnomAD database, including 13,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1091 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12531 hom.)
• Consequence: TRAPPC9 NM_001160372.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -3.33
• Publications: 16 publications found

Genes affected

TRAPPC9 (HGNC:30832): (trafficking protein particle complex subunit 9) This gene encodes a protein that likely plays a role in NF-kappa-B signaling. Mutations in this gene have been associated with autosomal-recessive cognitive disability. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2010]

TRAPPC9 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 13

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• intellectual disability-obesity-brain malformations-facial dysmorphism syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 8-140252916-G-A is Benign according to our data. Variant chr8-140252916-G-A is described in ClinVar as Benign. ClinVar VariationId is 130625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.33 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001160372.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC9	NM_001160372.4	MANE Select	c.2292C>T	p.Gly764Gly	synonymous	Exon 16 of 23	NP_001153844.1	Q96Q05-1
	TRAPPC9	NM_001374682.1		c.2313C>T	p.Gly771Gly	synonymous	Exon 17 of 24	NP_001361611.1
	TRAPPC9	NM_031466.8		c.2292C>T	p.Gly764Gly	synonymous	Exon 16 of 23	NP_113654.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAPPC9	ENST00000438773.4	TSL:1 MANE Select	c.2292C>T	p.Gly764Gly	synonymous	Exon 16 of 23	ENSP00000405060.3	Q96Q05-1
	TRAPPC9	ENST00000520857.5	TSL:1	c.1821C>T	p.Gly607Gly	synonymous	Exon 14 of 21	ENSP00000430116.1	H0YBR0
	TRAPPC9	ENST00000521667.5	TSL:1	n.697C>T		non_coding_transcript_exon	Exon 5 of 12

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16065 AN: 152044 Hom.: 1084 Cov.: 32

Gnomad AFR AF: 0.0354

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0699

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.0999

GnomAD2 exomes AF: 0.128 AC: 31915 AN: 249722 AF XY: 0.123

Gnomad AFR exome AF: 0.0342

Gnomad AMR exome AF: 0.244

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.00224

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.131

Gnomad OTH exome AF: 0.124

GnomAD4 exome AF: 0.124 AC: 181349 AN: 1460942 Hom.: 12531 Cov.: 32 AF XY: 0.123 AC XY: 89092 AN XY: 726766

African (AFR) AF: 0.0284 AC: 950 AN: 33476

American (AMR) AF: 0.235 AC: 10508 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2852 AN: 26128

East Asian (EAS) AF: 0.00164 AC: 65 AN: 39700

South Asian (SAS) AF: 0.0775 AC: 6686 AN: 86234

European-Finnish (FIN) AF: 0.170 AC: 9029 AN: 53148

Middle Eastern (MID) AF: 0.0827 AC: 473 AN: 5718

European-Non Finnish (NFE) AF: 0.130 AC: 144115 AN: 1111474

Other (OTH) AF: 0.111 AC: 6671 AN: 60366

GnomAD4 genome AF: 0.106 AC: 16083 AN: 152162 Hom.: 1091 Cov.: 32 AF XY: 0.108 AC XY: 8004 AN XY: 74384

African (AFR) AF: 0.0354 AC: 1472 AN: 41532

American (AMR) AF: 0.172 AC: 2625 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3466

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5178

South Asian (SAS) AF: 0.0697 AC: 336 AN: 4818

European-Finnish (FIN) AF: 0.179 AC: 1894 AN: 10570

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9041 AN: 67996

Other (OTH) AF: 0.0984 AC: 208 AN: 2114

Alfa AF: 0.121 Hom.: 2034

Bravo AF: 0.102

Asia WGS AF: 0.0590 AC: 207 AN: 3478

EpiCase AF: 0.124

EpiControl AF: 0.120

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Inborn genetic diseases (1)
-	-	1	Intellectual Disability, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.085
DANN	Benign	0.50
PhyloP100		-3.3
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11166965; hg19: chr8-141263015;